Friday, 12 February 2010

We remain sceptical about this theory; venous outflow obstruction does not explain the epidemiology of MS and falls down short on many other observations.

The interventions required to relieve venous obstruction are not without risks. The 'blood blockage theory' remains a theory and any involvement with the theory should be via ethically approved research studies.

Biogen-Idec and Elan have announced the eminent start of a clinical trial, called Surpass, to assess the effectiveness of switching to natalizumab (Tysabri) in patients that have experienced disease breakthrough with either glatiramer acetate or interferon beta.

I interpret this as a show of confidence by the companies that we can overcome the PML problem; there are now 31 confirmed cases of post-marketing PML in patients with MS receiving natalizumab.

After our MS Research Day on the 30th January we have been asked by several people about the correct dose of vitamin D to take to try and prevent MS and related disorders. Unfortunately we don't know. Until we do the appropriate clinical trials any recommendations will not be evidence-based. At present we defer to the Vitamin D Council's recommendations (www.vitamindcouncil.org):

".... if you have little UVB exposure, my advice is as follows: healthy children under the age of 1 years should take 1,000 IU per day—over the age of 1, 1,000 IU per every 25 pounds of body weight per day. Well adults and adolescents should take 5,000 IU per day....."

Before starting vD supplementation at this level we would urge you to see your doctor to discuss things formally; ideally this should be done in conjunction with blood monitoring.

Saturday, 6 February 2010

I received a strongly worded email criticising our site for participating in placebo-controlled MS clinical trials; in the opinion of the critic as there are licensed disease-modifying therapies for people with MS, placebo-controlled trials are unethical.

What do you think?

I responded as follows:
“Yes, there are several ethical considerations that need to be taken into account in relation to placebo-controlled MS trials; this issue has been extensively debated and discussed in the literature and there are International guidelines on the conduct of placebo-controlled trials.

In the UK, ethics committees make us insert a statement in the patient information sheet stating that there are licensed therapies and that by participating in a particular study people with MS could be denying themselves active treatment. In addition, we have to reconsent study participants after each relapse and/or confirmed disease progression. In addition, contemporary placebo-controlled trials have rescue arms, which allow study subjects active treatment within a study if their disease becomes active.

It is important to recognise that despite there being licensed therapies some patients don’t want to go onto them because they are injectables; if we did all trials with an active comparator, i.e. an injectable, we would exclude these patients from participating. People with needle phobia and those that have failed injectables because of side effects make up the majority of patients volunteering for placebo-controlled trials. I suspect, however, that once oral therapies are licensed for MS it will become very difficult to recruit subjects for placebo-controlled trials.

The issue of placebo-controlled trials should also be viewed on the background of the limited efficacy of the current injectables and the fact that we still don’t have data on whether or not they impact on the long-term prognosis of the disease.

In summary, I don’t think it is unethical to do placebo-controlled trials. However, you have to do them with carefully designed trials and informed consent. People with MS are perfectly capable of making an informed decision about not taking up the option of going on to a moderately effective first-line therapy and volunteering for a placebo-controlled trial of a new agent. At the end of the day we need to be pragmatic; without clinical trials we won’t advance the field and people living with MS are very aware of this. “

Monday, 1 February 2010

On the 22nd January the FDA approved dalfampridine (Ampyra, Elan/Acorda Therapeutics) extended-release tablets to improve walking in people with MS. Dalfampridine is a potassium channel blocker, that has been shown to improve walking speeds vs placebo. The drug was previously known as fampridine sustained release. Given at doses greater than the recommended 10 mg twice a day, dalfampridine can cause seizures. The most common adverse events reported in clinical trials were urinary tract infection, insomnia, dizziness, headache, nausea, weakness, back pain, balance disorder, swelling in the nose or throat, constipation, diarrhoea, indigestion, throat pain, and burning, tingling, or itching of skin. Dalfampridine, should not be used in patients with moderate or severe kidney disease. In these patients, blood levels with the drug approach those associated with the occurrence of seizures.

Please see previous posting below discussing the concerns with dalfampridine.

PML Risk Infographic

Holistic Management of MS ver. 7.0

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